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Annals of the Rheumatic Diseases Jan 2024Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several...
BACKGROUND
Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update.
METHODS
Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations.
RESULTS
Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV.
CONCLUSIONS
In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.
Topics: Humans; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Azathioprine; Cyclophosphamide; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Remission Induction; Rituximab; Practice Guidelines as Topic
PubMed: 36927642
DOI: 10.1136/ard-2022-223764 -
Lancet (London, England) Feb 2024Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis consists of two main diseases, granulomatosis with polyangiitis and microscopic polyangiitis, and... (Review)
Review
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis consists of two main diseases, granulomatosis with polyangiitis and microscopic polyangiitis, and remains among the most devastating and potentially lethal forms of autoimmune inflammatory disease. Granulomatosis with polyangiitis and microscopic polyangiitis are characterised by a necrotising vasculitis that can involve almost any organ, and have generally been studied together. The diseases commonly affect the kidneys, lungs, upper respiratory tract, skin, eyes, and peripheral nerves. Granulomatous inflammation and multinucleated giant cells are key pathological hallmarks of granulomatosis with polyangiitis, but are absent in microscopic polyangiitis. Many immune system events are essential to disease aetiopathogenesis, such as activation of the alternative complement pathway, neutrophil activation via complement receptors, and the influx of inflammatory cells, including monocytes and macrophages. These cells perpetuate inflammation and lead to organ damage. During the 21st century, the management of ANCA-associated vasculitis has moved away from reliance on cytotoxic medications and towards targeted biological medications for both the induction and maintenance of disease remission. Earlier diagnosis, partly the result of more reliable ANCA testing, has led to improved patient outcomes and better survival. Reductions in acute disease-related mortality have now shifted focus to long-term morbidities related to ANCA-associated vasculitis and their treatments, such as chronic kidney disease and cardiovascular disease. Therapeutic approaches in both clinical trials and clinical practice still remain too reliant on glucocorticoids, and continued efforts to reduce toxicity from glucocorticoids remain a priority in the development of new treatment strategies.
Topics: Humans; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Antibodies, Antineutrophil Cytoplasmic; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Autoimmune Diseases; Inflammation
PubMed: 38368016
DOI: 10.1016/S0140-6736(23)01736-1 -
Nephrology, Dialysis, Transplantation :... May 2024Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are characterized by small-vessel necrotizing inflammation, and prior to the advent of... (Review)
Review
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are characterized by small-vessel necrotizing inflammation, and prior to the advent of immunosuppressive therapy frequently had a fatal outcome. Treatment has transformed AAV into a relapsing/remitting disease with increased drug-related toxicities and organ damage. The use of glucocorticoids, cyclophosphamide and immunosuppressives (including azathioprine, mycophenolate and methotrexate) was optimized through a sequence of clinical trials establishing a standard of care against which subsequent targeted therapies could be developed. Improved understanding of pathophysiology has supported the development of B-cell depletion and complement inhibition in granulomatosis with polyangiitis and microscopic polyangiitis, and interleukin 5 inhibition for eosinophilic granulomatosis with polyangiitis, leading to the approval of newer agents for these conditions. There has been an increased attention on minimizing the adverse effects of treatment and on understanding the epidemiology of comorbidities in AAV. This review will focus on recent evidence from clinical trials, especially with respect to glucocorticoids, avacopan, plasma exchange, rituximab and mepolizumab, and their interpretation in the 2022 management recommendations by the European League of Associations of Rheumatology.
Topics: Humans; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Immunosuppressive Agents; Glucocorticoids; Standard of Care
PubMed: 37947275
DOI: 10.1093/ndt/gfad237 -
Nephrology, Dialysis, Transplantation :... Oct 2023Updated guidelines on the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were released in 2021 by the American College of...
Management of antineutrophil cytoplasmic antibody-associated vasculitis with glomerulonephritis as proposed by the ACR 2021, EULAR 2022 and KDIGO 2021 guidelines/recommendations.
Updated guidelines on the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were released in 2021 by the American College of Rheumatology jointly with the Vasculitis Foundation and, subsequently, in 2022 by the European Alliance of Associations for Rheumatology. In addition, in 2021, the Kidney Disease: Improving Global Outcomes had released updated recommendations on the treatment of AAV with glomerulonephritis (AAV-GN). Kidney involvement is particularly relevant in microscopic polyangiitis and granulomatosis with polyangiitis, but is less frequent in eosinophilic granulomatosis with polyangiitis. The management of AAV-GN has been a focus for drug development and change over the past 10 years. Avoidance of progression to end-stage kidney disease (ESKD) or kidney failure is one of the main unmet needs in the management of AAV, with ESKD having a major impact on morbidity, health costs and mortality risk. Relevant changes in AAV-GN management are related to remission-induction treatment of patients with severe kidney disease, the use of glucocorticoids and avacopan, and remission-maintenance treatment. All the documents provide guidance in accordance with the evidence-based standard of care available at the time of their release. With our work we aim to (i) show the progress made and identify the differences between guidelines and recommendations, (ii) discuss the supporting rationale for those, and (iii) identify gaps in knowledge that could benefit from additional research and should be revised in subsequent updates.
Topics: Humans; Antibodies, Antineutrophil Cytoplasmic; Granulomatosis with Polyangiitis; Churg-Strauss Syndrome; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; Glomerulonephritis; Kidney Failure, Chronic
PubMed: 37164940
DOI: 10.1093/ndt/gfad090 -
Neuroimaging Clinics of North America Feb 2024Small artery vasculitis of the CNS is a rare and serious condition characterized by the inflammation of blood vessels within the brain and spinal cord. There are two... (Review)
Review
Small artery vasculitis of the CNS is a rare and serious condition characterized by the inflammation of blood vessels within the brain and spinal cord. There are two groups of small artery vasculitis determined by the presence or absence of immunoglobulin complex deposition in the vessel wall. The former includes anti-glomerular basement membrane disease, cryoglobulinemic vasculitis, and IgA vasculitis. Absence of immune complex deposition is associated with anti-neutrophil cytoplasmic antibody (ANCA) and includes microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and primary angiitis of the CNS. These conditions present a diagnostic challenge in which imaging plays a crucial role.
Topics: Humans; Granulomatosis with Polyangiitis; Churg-Strauss Syndrome; Microscopic Polyangiitis; Arteries; Antibodies, Antineutrophil Cytoplasmic
PubMed: 37951706
DOI: 10.1016/j.nic.2023.07.009 -
Rheumatic Diseases Clinics of North... Aug 2023We have made significant headway in our ability to induce and maintain remission in patients with granulomatosis with polyangiitis and microscopic polyangiitis. With... (Review)
Review
We have made significant headway in our ability to induce and maintain remission in patients with granulomatosis with polyangiitis and microscopic polyangiitis. With increased understanding of the pathogenesis of antineutrophilic cytoplasmic antibody-associated vasculitides (AAV), therapeutic targets have been identified and studied in clinical trials. From initial induction strategies including glucocorticoids and cyclophosphamide, we have discovered effective induction regimens with rituximab and complement inhibition that can significantly decrease the glucocorticoid cumulative doses in patients with AAV. There are many trials underway evaluating management strategies for refractory patients and exploring new and old therapies that may help to continuously improve outcomes for patients with AAV.
Topics: Humans; Microscopic Polyangiitis; Granulomatosis with Polyangiitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Remission Induction; Rituximab; Antibodies, Antineutrophil Cytoplasmic
PubMed: 37331732
DOI: 10.1016/j.rdc.2023.03.004 -
The Lancet. Rheumatology May 2024Proteinase 3 (PR3)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is one of two major ANCA-associated vasculitis variants and is... (Review)
Review
Proteinase 3 (PR3)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is one of two major ANCA-associated vasculitis variants and is pathogenically linked to granulomatosis with polyangiitis (GPA). GPA is characterised by necrotising granulomatous inflammation that preferentially affects the respiratory tract. The small vessel vasculitis features of GPA are shared with microscopic polyangiitis. Necrotising granulomatous inflammation of GPA can lead to PR3-ANCA and small vessel vasculitis via activation of neutrophils and monocytes. B cells are central to the pathogenesis of PR3-ANCA-associated vasculitis. They are targeted successfully by remission induction and maintenance therapy with rituximab. Relapses of PR3-ANCA-associated vasculitis and toxicities associated with current standard therapy contribute substantially to remaining mortality and damage-associated morbidity. More effective and less toxic treatments are sought to address this unmet need. Advances with cellular and novel antigen-specific immunotherapies hold promise for application in autoimmune disease, including PR3-ANCA-associated vasculitis. This Series paper describes the inter-related histopathological and clinical features, pathophysiology, as well as current and future targeted treatments for PR3-ANCA-associated vasculitis.
Topics: Humans; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Granulomatosis with Polyangiitis; Myeloblastin; Rituximab
PubMed: 38574742
DOI: 10.1016/S2665-9913(24)00035-3 -
Modern Rheumatology Mar 2024To revise the 2017 clinical practice guidelines (CPG) for the management of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) to reflect...
Clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of microscopic polyangiitis and granulomatosis with polyangiitis: The 2023 update - secondary publication.
OBJECTIVE
To revise the 2017 clinical practice guidelines (CPG) for the management of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) to reflect advancements in the field.
METHODS
Similar to the 2017 CPG, the Grading of Recommendations, Assessment, Development, and Evaluation system was adopted for this revision. The intended users of this CPG include patients diagnosed with MPA or GPA in Japan and their families and healthcare professionals, including specialists and non-specialists. Based on a scoping review, four clinical questions (CQs) of the 2017 guidelines were modified, and six new CQs were added.
RESULTS
We suggest a combination of glucocorticoid and cyclophosphamide or rituximab for remission induction therapy. In cases where cyclophosphamide or rituximab is used, we suggest the use of avacopan over high-dose glucocorticoid. Furthermore, we suggest against the use of plasma exchange in addition to the standard treatment in severe cases of MPA/GPA. Finally, we suggest the use of glucocorticoid and rituximab over glucocorticoid and azathioprine for remission maintenance therapy.
CONCLUSIONS
The recommendations have been updated based on patient preference, certainty of evidence, benefit and risk balance, and cost.
Topics: Humans; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Cyclophosphamide; Glucocorticoids; Granulomatosis with Polyangiitis; Immunosuppressive Agents; Japan; Microscopic Polyangiitis; Rituximab
PubMed: 37599461
DOI: 10.1093/mr/road081